Introduction
For therapeutic and cosmetic efficacy, skin penetration properties of dermal formulations are crucial. Rate and extend of active ingredients reaching the site of action e.g. the horny layer, the living epidermis or dermis has become more and more important. To date the lack of analytical methods for measuring penetration properties of drugs in vivo is challenging. Tape stripping is one of the traditional investigative techniques of the past. Due to major methodological shortcomings as high variability and low measurement depth, there is a great need for new and more reliable methods. Now it has been shown that Confocal Raman Microspectroscopy (CRS) is suitable for the non-invasive evaluation of topical products in vivo. Proderm is proud to offer this new CRS technology with all its possibilities.
Advantages of CRS
CRS is an optical method to determine the chemical composition of the skin in vivo. The combination of spontaneous Raman scattering emission with a confocal signal collection scheme enables data acquisition with a notable high spatial resolution. This makes it possible to monitor the cutaneous transport of topically applied compounds in vivo in real time. The none-destructive nature of this method is not only less stressful for the study participants, it also allows for continuous measurements. It is possible to measure the depth of the penetration of a dermatological product into the stratum corneum (SC) as well as the shape of distribution profiles of substances. Further the depletion of substances from SC into the viable epidermis can be assessed. This is a measure of the permeation rate of a substance into the living epidermis. Additionally skin hydration level and the thickness of the stratum corneum can be estimated. Compared to tape stripping CRS is not only more reliable, it is also saving time and resources since tape stripping is very time and labour intensive. While tape stripping only samples part of the stratum corneum, CRSs is able to detect deeper inside the skin covering the stratum corneum completely. For active substances to be effective, it is not solely important that they reach the active site, they also have to be present in a form that allows them to be therapeutically available. Usually they need to be in solution instead of being crystalized out. Other than tape stripping, CRS is able to discriminate between the two forms, adding value to the interpretation of the results and performance claims. Compared to other techniques CRS does not rely on labels or dyes and direct drug quantification is feasible. CRS test results are reliable, reproducible and correlate with data from the well established in vitro permeation test (IVPT) model using human epidermis.
The possibility of CRS to compare the skin uptake of two substances makes it suitable for the evaluation of topical bioequivalence. It can even be used to discriminate between and evaluate complex topical formulations. This has recently been shown for the delivery of diclofenac sodium from two dermatological drug products. This is important, since commercially available dermatological products are often composed of a variety of complex ingredients including penetration enhancers.
proderm offers CRS penetration studies for diclofenac formulations
With its anti-inflammatory, analgesic and antipyretic properties, diclofenac is a common active in topical drugs to treat chronic pain. Topical diclofenac products have the advantage, that they enable local treatment of pain and inflammation while minimizing systemic absorption and side effects. There is a wide range of topical diclofenac products including gels, ointments, creams, lotions and plasters. The assessment of the bioavailability of topical applied diclofenac for in vivo skin research and claims support is challenging. A recent publication shows that CRS is well suitable to successfully measure and compare diclofenac penetration rates of different topical formulations in clinical studies with small case numbers.
